Farah Aleisa, MD
The HERMES meta-analysis demonstrated the benefit of second-generation endovascular recanalization therapies (primarily stent retrievers) over medical therapy alone among patients with acute ischemic stroke due to large vessel occlusions.1,2,3 The utilization of brain imaging to exclude patients with a large core of infarcted brain tissue in this pooled analysis was based on selection of patients with an initial Alberta Stroke Program Early CT Score (ASPECTS) of 6 or more.4,5 However, we don’t have large studies looking for the benefits of mechanical thrombectomy (MT) with large core ischemic stroke (ASPECTS <6). The available subgroup analyses in the literature concerning thrombectomy for large core stroke reported rates of symptomatic intracerebral hemorrhage ranging from 16% to 31%.6-10 This study was done to address the uncertainties regarding the associated benefits and risks of MT for patients who had large core ischemic stroke by recognizing the clinical and imaging factors associated with good clinical outcomes.
The data in this study was collected from the multicentric stroke registry for acute ischemic stroke patients treated with MT. Baseline large ischemic core was defined as diffusion-weighted imaging (DWI)–ASPECTS of ≤5. The degree of disability was assessed by the modified Rankin Scale at 90 days. Outcomes included good outcome (modified Rankin Scale score of ≤2) and mortality (modified Rankin Scale score of 6).
Of the 216 patients with a baseline ASPECT score of ≤5 (mean DWI volume 94±66.5 mL) treated with MT, a total of 127 patients presented a DWI-positive lesional volume larger than 70 mL and 73 a volume larger than 100 mL. Baseline independent predictors of decreased chance of good outcome, irrespectively of treatment-related variables, were age (adjusted-OR for every 10 years increase, 0.67; 95% CI, 0.53–0.85; P=0.001) and DWI-positive volume (OR, 0.98; 95% CI, 0.97–0.99; P<0.001). Successful recanalization (adjusted OR, 4.56; 95% CI, 1.79–11.62; P<0.001) was found to be an independent predictor of good outcome. Independent predictor of 90-day mRS score of 0–2 in the DWI volume ≥100 mL subgroup were procedure length (OR, 0.96; 95% CI, 0.92–0.99; P=0.024), while increasing DWI-positive lesion volume showed a trend but did not reach statistical significance (OR, 0.30; 95% CI, 0.09–1.0; P=0.053). Further, increase in DWI volume (OR, 1.03; 95% CI, 1–1.05; P=0.010) and PH1-2 hemorrhagic transformation (OR, 32.8; 95% CI, 3.5– 309.5; P=0.002) independently predicted 90-day mortality.
This study reaffirmed previous MT subgroup analyses findings from major large randomized clinical trials that showed an association between larger baseline core volumes with worse clinical outcomes and higher mortality. They looked for independent outcome predictors for patients affected by DWI-positive lesions larger than 70 and 100 mL, respectively, cutoffs which have consistently shown to be associated with poor outcome and the so-called malignant profile. In this study, DWI-ASPECT score is the most reliable predictor in large strokes both from the preprocedural and postprocedural settings. This study was the largest reported series evaluating DWI volume ischemic lesions on large volume stroke patients treated with MT. In the same study, no significant difference emerged in between recanalized versus nonrecanalized patients and between ischemic core extension and PH1-2 hemorrhagic transformation.
This study has a few limitations. First, it is a retrospective registry, although it has a large sample. Second, patient follow-up of 3 months might be considered a short duration to demonstrate effects in the clinical outcomes. Randomized controlled studies are needed in this subset of patients with large permanent ischemic core to investigate the benefit of MT.
References:
1. Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA. 1995;274:1017–1025.
2. Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998;352:1245–1251.
3. Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA. 1999;282:2019–2026.
4. Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, et al; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372:1009–1018. doi: 10.1056/NEJMoa1414792
5. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, et al; SWIFT PRIME Investigators. Stentretriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015;372:2285– 2295. doi: 10.1056/NEJMoa1415061
6. Thijs VN, Lansberg MG, Beaulieu C, Marks MP, Moseley ME, AlbersGW. Is early ischemic lesion volume on diffusion-weighted imaging an independent predictor of stroke outcome? A multivariable analysis. Stroke. 2000;31:2597–2602.
7. Lansberg MG, Thijs VN, Bammer R, Kemp S, Wijman CA, Marks MP, et al; DEFUSE Investigators. Risk factors of symptomatic intracerebral hemorrhage after tPA therapy for acute stroke. Stroke. 2007;38:2275–2278. doi: 10.1161/STROKEAHA.106.480475
8. Kimura K, Iguchi Y, Shibazaki K, Terasawa Y, Inoue T, Uemura J, et al. Large ischemic lesions on diffusion-weighted imaging done before intravenous tissue plasminogen activator thrombolysis predicts a poor outcome in patients with acute stroke. Stroke. 2008;39:2388–2391. doi: 10.1161/STROKEAHA.107.510917
9. Albers GW, Thijs VN, Wechsler L, Kemp S, Schlaug G, Skalabrin E, et al; DEFUSE Investigators. Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. Ann Neurol. 2006;60:508–517. doi: 10.1002/ana.20976
10. Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, et al; HERMES Collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387:1723–1731. doi: 10.1016/S0140-6736(16)00163-X
